The Program Project Grant (PPG) extends prior studies by the investigators on neuronal and muscular activity-dependent plasticity associated with locomotion following a complete thoracic spinal cord injury (SCI). The three Research Proposals and supportive Core Projects together, will help identify factors that limit locomotor recovery after SCI and elements that may be promoted through physical and biological interventions to enhance the function of persons with SCI. We will address issue ranging from mechanisms for regulation of protein expression in muscle fibers and neurons of rats to optimization of rehabilitation procedures for SCI patients. A project assesses neurotrophic and electro-mechanical influences on the regulation of muscle mass, protein expression, phenotype and function in rats after lower spinal cord isolation. A project examines adaptations of inhibitory neurotransmitters, glycine and GABA, in flexor and extensor spinal pathways associated with spinal rats learning to step or stand. A project studies the effect of kinetics and kinematics on the motor output of the lower extremities during weight-supported stepping and how sensory information can be used to optimize the recovery of locomotion of SCI patients. Projects parallels aspects of in investigation of muscle adaptations and in study of the effects of step training on neuronal activity. The Administrative Core I coordinates all organizational, personnel and budgetary aspects of the PPG. The Animal Core coordinates animal surgeries, training and provides premium care for control and SCI rats for Projects. The 11 scientists participating are from UCLA and UCI. Four UCLA Departments, Biomathematics, Biostatistics, Neurology and Physiological Science will participate with support from the Brain Research Institute which has administered the PPG since 1980. The long term objectives of the PPG continue to be the identification of the 1) physiological and molecular mechanisms for inducing use-dependent neural and muscular plasticity associated with SCI and 2) optimal procedures for functional recovery after SCI. The inability to fully bear weight during standing and stepping, the inability to initiate swing, and the absence of weight bearing on the muscle can be key deficits following SCI. Identification of such limiting factors associated with flexion and extension are essential to understanding the mechanisms of motor recovery following SCI. These factors will be studied using a combination of behavioral, physiological and biochemical approaches.